Self-Limiting Sub-5 nm Nanodiamonds by Geochemistry-Inspired Synthesis.

Controlling diamond structures with nanometer precision is fundamentally challenging owing to their extreme and far-from-equilibrium synthetic conditions. State-of-the-art techniques, including detonation, chemical vapor deposition, mechanical grinding, and high-pressure-high-temperature synthesis, yield nanodiamond particles with a broad distribution of sizes. Despite many efforts, the direct synthesis of nanodiamonds with precisely controlled diameters remains elusive. Here the geochemistry-inspired synthesis of sub-5 nm nanodiamonds with sub-nanometer size deviation is described. High-pressure-high-temperature treatment of uniform iron carbide nanoparticles embedded in iron oxide matrices yields nanodiamonds with tunable diameters down to 2.13 and 0.22 nm standard deviation. A self-limiting, redox-driven, and diffusion-controlled solid-state reaction mechanism is proposed and supported by in situ X-ray diffraction, ex situ characterizations, and computational modeling. This work provides a unique mechanism for the precise control of nanostructured diamonds under extreme conditions and paves the road for the full realization of their potential in emerging technologies.

Use of Audio Computer-Assisted Self-Interviews to Gather Information on Risk Behaviors in a Population of Pregnant Adolescents.

In a prospective study comparing the use of the Audio Computer-Assisted Self-Interview (ACASI) with a traditional clinical interview in 40 pregnant adolescents, there was significantly greater disclosure of violence with the ACASI method. Better identification of high-risk behaviors may help to optimize care and programing for pregnant adolescents.

Online Calculator to Improve Counseling of Short-Term Neonatal Morbidity and Mortality Outcomes at Extremely Low Gestational Age (23-28 Weeks).

Objective Extremely low gestational age (ELGA) infants are at high risk of perinatal and neonatal morbidity and mortality. Accurate and relevant data are essential for developing a health care plan and providing realistic estimates of infants' outcomes. Study Design Retrospective analysis of all infants delivered between 23(0/7) and 28(6/7) weeks' gestation over 11 years at a single center. Using logistic regression analysis, gestational age (GA)-specific mortality and morbidity rates, and the effects of gender, antenatal corticosteroids, multiple gestation, and birth weight (BW) were determined. Results Of the 766 study infants, 644 (84.1%) were admitted to the neonatal intensive care unit, of which 502 (75.8%) survived to discharge. GA, antenatal corticosteroids, and BW were significant predictors of survival (GA: odds ratio [OR] = 1.83, 95% confidence interval [CI] = 1.64-2.04; corticosteroids: OR = 7.62, 95% CI = 5.19-11.18; BW: OR = 1.56, 95% CI = 1.44-1.69). Increasing BW correlated with a decreasing mortality rate. Conclusion This study provides recent outcome data of ELGA infants delivered at a tertiary level center. The results have been translated into an online counseling tool (http://murmuring-brook-6600.herokuapp.com/ELGA.html).

Image-guided video assisted thoracoscopic surgery (iVATS) - phase I-II clinical trial.

PURPOSE: To facilitate localization and resection of small lung nodules, we developed a prospective clinical trial (ClinicalTrials.gov number NCT01847209) for a novel surgical approach which combines placement of fiducials using intra-operative C-arm computed tomography (CT) guidance with standard thoracoscopic resection technique using image-guided video-assisted thoracoscopic surgery (iVATS). METHODS: Pretrial training was performed in a porcine model using C-arm CT and needle guidance software. Methodology and workflow for iVATS was developed, and a multi-modality team was trained. A prospective phase I-II clinical trial was initiated with the goal of recruiting eligible patients with small peripheral pulmonary nodules. Intra-operative C-arm CT scan was utilized for guidance of percutaneous marking with two T-bars (Kimberly-Clark, Roswell, GA) followed by VATS resection of the tumor. RESULTS: Twenty-five patients were enrolled; 23 underwent iVATS, one withdrew, and one lesion resolved. Size of lesions were: 0.6-1.8 cm, mean = 1.3 ± 0.38 cm.. All 23 patients underwent complete resection of their lesions. CT imaging of the resected specimens confirmed the removal of the T-bars and the nodule. Average and total procedure radiation dose was in the acceptable low range (median = 1501 µGy*m(2), range 665-16,326). There were no deaths, and all patients were discharged from the hospital (median length of stay = 4 days, range 2-12). Three patients had postoperative complications: one prolonged air-leak, one pneumonia, and one ileus. CONCLUSIONS: A successful and safe step-wise process has been established for iVATS, combining intra-operative C-arm CT scanning and thoracoscopic surgery in a hybrid operating room.

Delayed clinical and ex vivo response to mammalian meat in patients with IgE to galactose-alpha-1,3-galactose.

BACKGROUND: In 2009, we reported a novel form of delayed anaphylaxis to red meat related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Although patients were remarkably consistent in their description of a 3- to 6-hour delay between eating mammalian meat and the appearance of symptoms, this delay has not been demonstrated under observed studies. OBJECTIVES: We sought to formally document the time course of clinical symptoms after the ingestion of mammalian meat in subjects with IgE to alpha-gal and to monitor ex vivo for the appearance of markers of an allergic reaction. METHODS: Open food challenges were performed with mammalian meat in 12 subjects with a history of severe urticarial reactions 3 to 6 hours after eating beef, pork, or lamb, as well as in 13 control subjects. Blood samples were taken hourly during each challenge. RESULTS: Ten of 12 subjects with IgE to alpha-gal had clinical evidence of a reaction during the food challenge (vs none of the control subjects, P < .001). The reactions occurred 3 to 7 hours after the initial ingestion of mammalian meat and ranged from urticaria to anaphylaxis. Tryptase levels were positive in 3 challenges. Basophil activation, as measured by increased expression of CD63, correlated with the appearance of clinical symptoms. CONCLUSION: The results presented provide clear evidence of an IgE-mediated food allergy that occurs several hours after ingestion of the inciting allergen. Moreover, here we report that in vivo basophil activation during a food challenge occurs in the same time frame as clinical symptoms and likely reflects the appearance of the antigen in the bloodstream.

Non-invasive prenatal testing: ethics and policy considerations.

New technologies analyzing fetal DNA in maternal blood have led to the wide commercial availability of non-invasive prenatal testing (NIPT). We present here for clinicians the ethical and policy issues related to an emerging practice option. Although NIPT presents opportunities for pregnant women, particularly women who are at increased risk of having a baby with an abnormality or who are otherwise likely to access invasive prenatal testing, NIPT brings significant ethics and policy challenges. The ethical issues include multiple aspects of informed decision-making, such as access to counselling about the possible results of the test in advance of making a decision about participation in NIPT. Policy considerations include issues related to offering and promoting a privately available medical strategy in publicly funded institutions. Ethics and policy considerations merge in NIPT with regard to sex selection and support for persons living with disabilities.

Les nouvelles techniques qui font appel à l'analyse de l'ADN fœtal dans le sang maternel ont mené à l'élargissement de la disponibilité commerciale du dépistage prénatal non effractif (DPNE). Nous présentons ici, à l'intention des cliniciens, les questions d'éthique et de politique qui sont associées à une option de pratique émergente. Bien que le DPNE offre des possibilités aux femmes enceintes (et particulièrement aux femmes qui sont exposées à des risques accrus de donner naissance à un enfant présentant une anomalie ou qui sont autrement susceptibles d'avoir recours au dépistage prénatal effractif), il donne lieu à des défis considérables en matière d'éthique et de politique. Les multiples aspects de la prise d'une décision éclairée (comme l'accès à des services de counseling au sujet des résultats possibles du test avant la prise d'une décision quant à la participation au DPNE) font partie des enjeux éthiques. Parmi les considérations en matière de politique, on trouve les questions liées à l'offre et à la promotion, au sein d'établissements subventionnés par l'État, d'une stratégie médicale offerte au privé. Les considérations en matière d'éthique et de politique s'entremêlent dans le cas du DPNE, pour ce qui est des questions relevant de la sélection du sexe et de l'offre d'un soutien aux personnes qui vivent avec des incapacités.

Pediatric and Adolescent Gynecology WebEd: A Brief Report of an Underutilized Online Learning Module.

Pediatric and adolescent gynecology (PAG) is a unique subspecialty for which accessible educational resources and clinical exposure have historically been limited; surveys show that trainees in both obstetrics and gynecology and pediatrics agree. In 2014, the North American Society for Pediatric and Adolescent Gynecology (NASPAG) introduced PAG WebEd, an original and interactive online case-based curriculum designed to bridge this learning gap. As of 2023, there are 35 published PAG WebEd clinical cases with key learning points that present, test, and discuss a variety of current PAG topics. The NASPAG Resident Education Committee (REC) compiled and reviewed administrative data from the module platform to investigate trainee utilization and performance. The activity data and assessment scores for 161 registered users are included and reported in this article. This brief report highlights that a relatively small number of medical trainees use PAG WebEd and aims to raise awareness of this resource through publication. There is potential for many more users to benefit from this resource; its efficacy as an examination and clinical practice tool could also be measured. The NASPAG REC hopes to ultimately show, with increased utilization, that PAG WebEd deserves to be a key piece of PAG-focused medical education. For PAG WebEd information and faculty registration, as well as a link that allows faculty to submit new learners, please visit https://www.naspag.org/pagwebed-information.

Resident Education Curriculum in Pediatric and Adolescent Gynecology: The Short Curriculum 4.0.

Exposure to pediatric and adolescent gynecology (PAG) varies across residency programs in obstetrics and gynecology, family medicine, and pediatrics, as well as both adolescent medicine and PAG fellowship programs. Nevertheless, these programs are responsible for training residents and fellows and providing opportunities to fulfill PAG learning objectives. To that end, the North American Society for Pediatric and Adolescent Gynecology has taken a leadership role in PAG trainee education by creating and maintaining this Short Curriculum. The curriculum outlines specific learning objectives central to PAG education and lists high-yield, concise resources for learners. This updated curriculum replaces the previous 2021 publication with a new focus toward accessible online content and updated resources.

Keeping the patient focus: using tablet technology to enhance education and practice.

Nurses are busy. Technology places a vast amount of information at their fingertips.

Case Report of the Successful Use of Mirena Levonorgestrel Intrauterine System in a Patient with Didelphys Uterus and Obstructed Hemivagina.

BACKGROUND: The Mirena levonorgestrel intrauterine system (IUS; Bayer HealthCare Pharmaceuticals) is frequently used for menstrual suppression in adolescents with special needs. However, the presence of a uterine anomaly is generally considered a contraindication to IUS insertion, thereby excluding a potentially highly effective option for this patient population. CASE: A Mirena IUS was used in a medically and surgically complex special needs 14-year-old adolescent with a didelphys uterus and obstructed hemivagina. With the IUS inserted into the unobstructed uterus, she achieved amenorrhea and significant reduction in pain, with interval reduction in hematometra in the contralateral obstructed uterus. SUMMARY AND CONCLUSION: We report the successful use of the Mirena IUS in a patient with a Müllerian anomaly, supporting the use of this device in carefully selected patients.

Identification of immunologic and pathologic parameters of death versus survival in respiratory tularemia.

Francisella tularensis can cause severe disseminated disease after respiratory infection. The identification of factors involved in mortality or recovery following induction of tularemia in the mouse will improve our understanding of the natural history of this disease and facilitate future evaluation of vaccine candidate preparations. BALB/c mice were infected intranasally with the live vaccine strain (LVS) of F. tularensis subsp. holarctica and euthanized at different stages of disease to analyze the induction of immune molecules, gross anatomical features of organs, bacterial burdens, and progression of the histopathological changes in lung and spleen. Tissue-specific interleukin-6 (IL-6), macrophage inflammatory protein 2, and monocyte chemotactic protein 1 were immune markers of mortality, while anti-LVS immunoglobulin M and IL-1beta were associated with survival. Moribund mice had enlarged spleens and lungs, while surviving mice had even more prominent splenomegaly and normal-appearing lungs. Histopathology of the spleens of severely ill mice was characterized by disrupted lymphoid follicles and fragmented nuclei, while the spleens of survivors appeared healthy but with increased numbers of megakaryocytes and erythrocytes. Histopathology of the lungs of severely ill mice indicated severe pneumonia. Lungs of survivors at early time points showed increased inflammation, while at late times they appeared healthy with peribronchial lymphoid aggregates. Our results suggest that host immune factors are able to affect bacterial dissemination after respiratory tularemia, provide new insights regarding the pathological characteristics of pulmonary tularemia leading to systemic disease, and potentially identify immune markers associated with recovery from the disease.

Community awareness of stroke, hypertension and modifiable risk factors for cardiovascular disease in Nkonya-Wurupong, Ghana.

Hypertension and other non-communicable diseases are growing risk factors for cardiovascular disease and stroke in lowand middle-income countries like Ghana who are experiencing the effects of rapid urbanization and globalization. Awareness and education may help reduce the population's exposure to modifiable risk-factors. A survey from a central clinic outside the city of Ho, in the Volta region investigates participants' level of awareness and education surrounding hypertension and stroke. It provides important information about the approach to education and preventing modifiable risk factors. A central clinic in Nkonya-Wurupong, Ghana, evaluated 1671 patients in July 2016, and a group of 302 adults over the age of 18 provided a convenience sampling. The survey examined three main areas: demographics, medical history, and evaluation of knowledge with respect to stroke and cardiovascular risk factors. 18.5% of participants demonstrated hypertension (BP ³ 140/90). 30% of those with hypertension were female. Thirty-five percent believed hypertension was a risk factor for stroke, and only 26% were currently medicated for hypertension. Poor diet, obesity and alcohol were the most frequently identified risk factors for stroke and 86% of participants felt that it was preventable. However, diet, heart disease, smoking, obesity, diabetes, sedentary lifestyle or alcohol were not uniformly identified as stroke risk factors. One-sided weakness was the only symptom the group associated with stroke. Other symptoms included in the survey were headache, slurred speech, visual changes, dizziness, and facial droop. Educational resources included TV, school, internet, radio, medical books and health professionals and 7% responded that they had never been educated about stroke and its risk-factors. Knowledge of hypertensive consequences including cardiovascular disease and stroke varies significantly along with stroke identification and educational sources. However, many indicated that stroke is due to lifestyle and can be prevented. It is unclear what respondents believe these lifestyle choices are. This data suggests there are major areas where healthcare education is needed. Discerning baseline health in developing countries will become increasingly important when evaluating an area for health resource allocation including patient health education programs.

Laparoscopic Radical Trachelectomy for Embryonal Rhabdomyosarcoma of the Cervix in a 2-Year-Old Girl.

BACKGROUND: Embryonal rhabdomyosarcoma of the cervix is a rare and aggressive malignancy that usually affects children and young adults. CASE: We describe a 2-year-old patient who presented with a mass protruding through the vaginal introitus. Preoperative investigations including vaginoscopy, hysteroscopy, magnetic resonance imaging, and biopsies confirmed embryonal rhabdomyosarcoma, botryoid subtype, arising from the cervix. She was successfully treated with neoadjuvant chemotherapy and interval laparoscopic radical trachelectomy to achieve remission. CONCLUSION: Collaboration between the pediatric and adult surgical and medical oncology teams was critical to implement this fertility-sparing treatment strategy in such a young girl having this rare tumor.

Prevalence of elevated body mass index and blood pressure in a rural school-aged population: implications for school nurses.

The growing prevalence of overweight in students and adolescents has become a matter of national concern and is linked to a rise in chronic health conditions in students who previously had low prevalence rates, such as cardiovascular disease. This study examined the relationships between age, ethnicity, race, body mass index (BMI), and elevated blood pressure (BP) in a rural school age population. Data are reported for 1121 students in grades K-11. The sample was 55% African American, 41% Caucasian, 3% Hispanic, and 1% other. The prevalence of students at risk of being overweight (BMI > or =85th percentile) was 46.5%, and the prevalence of overweight students (BMI > or =95th percentile) was 29.1%. The prevalence of elevated BP was 21.6%. Elevated BMI and BP were more prevalent in older students. While there was a direct relationship between elevated BMI and elevated BP for all groups, African Americans were more likely to have an elevated BP with a normal BMI. These findings demonstrate the important role of the school nurse in providing effective prevention strategies related to screening, follow-up, and treatment.

Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling.

TLR2 plays a key role in the initiation of the cellular innate immune responses by a wide range of bacterial products. TLRs signaling, including TLR2 and its coreceptors TLR1 and TLR6, is mediated by a number of specific ligands. Although many of the TLR-mediated cell signaling pathways have been elucidated in the past few years, the molecular mechanisms that lead to cell activation are still poorly understood. In this study, we investigate the interaction of PorB from Neisseria meningitidis with TLR2 and describe the direct binding of a bacterial protein to TLR2 for the first time. Using labeled PorB, we demonstrate its binding to TLR2 both in its soluble form in vitro, and when it is over-expressed on the surface of human embryonic kidney 293 cells. We also show that TLR2-mediated binding of PorB is directly related to cellular activation. In addition, using 293 cells expressing the chimeric TLR2/TLR1 and TLR2/TLR6 complexes, we report the selectivity of PorB binding to the TLR2/TLR1 heterodimer, which is required for initiating signaling in transfected 293 cells and in murine B cells. Together, these data provide new evidence that TLR2 recognizes PorB through direct binding, and that PorB-induced cell activation is mediated by a TLR2/TLR1 complex.

Improved purification of native meningococcal porin PorB and studies on its structure/function.

The outer membrane protein PorB of Neisseria meningitidis is a pore-forming protein which has various effects on eukaryotic cells. It has been shown to (1) up-regulate the surface expression of the co-stimulatory molecule CD86 and of MHC class II (which are TLR2/MyD88 dependent and related to the porin's immune-potentiating ability), (2) be involved in prevention of apoptosis by modulating the mitochondrial membrane potential, and (3) form pores in eukaryotic cells. As an outer membrane protein, its native trimeric form isolation is complicated by its insoluble nature, requiring the presence of detergent throughout the whole procedure, and by its tight association with other outer membrane components, such as neisserial LOS or lipoproteins. In this study, an improved chromatographic purification method to obtain an homogeneous product free of endotoxin and lipoprotein is described, without loss of any of the above-mentioned properties of the porin. Furthermore, we have investigated the requirement of the native trimeric structure for the porin's activity. Inactivation of functional PorB trimers into non-functional monomers was achieved by incubation on ice. Thus, routine long- and medium-term storage at low temperature may be a cause of porin inactivation.

The gonococcal Fur-regulated tbpA and tbpB genes are expressed during natural mucosal gonococcal infection.

Iron is limiting in the human host, and bacterial pathogens respond to this environment by regulating gene expression through the ferric uptake regulator protein (Fur). In vitro studies have demonstrated that Neisseria gonorrhoeae controls the expression of several critical genes through an iron- and Fur-mediated mechanism. While most in vitro experiments are designed to determine the response of N. gonorrhoeae to an exogenous iron concentration of zero, these organisms are unlikely to be exposed to such severe limitations of iron in vivo. To determine if N. gonorrhoeae expresses iron- and Fur-regulated genes in vivo during uncomplicated gonococcal infection, we examined gene expression profiles of specimens obtained from male subjects with urethral infections. RNA was isolated from urethral swab specimens and used as a template to amplify, by reverse transcriptase PCR (RT-PCR), gonococcal genes known to be regulated by iron and Fur (tbpA, tbpB, and fur). The constitutively expressed gonococcal rmp gene was used as a positive control. RT-PCR analysis indicated that gonorrhea-positive specimens where rmp expression was seen were also 93% (51/55) fbpA positive, 87% (48/55) tbpA positive, and 86% (14 of 16 tested) tbpB positive. In addition, we detected a fur transcript in 79% (37 of 47 tested) of positive specimens. We also measured increases in levels of immunoglobulin G antibody against TbpA (91%) and TbpB (73%) antigens in sera from infected male subjects compared to those in uninfected controls. A positive trend between tbpA gene expression and TbpA antibody levels in sera indicated a relationship between levels of gene expression and immune response in male subjects infected with gonorrhea for the first time. These results indicate that gonococcal iron- and Fur-regulated tbpA and tbpB genes are expressed in gonococcal infection and that male subjects with mucosal gonococcal infections exhibit antibodies to these proteins.

Neisserial PorB is translocated to the mitochondria of HeLa cells infected with Neisseria meningitidis and protects cells from apoptosis.

We have previously shown that purified meningococcal porin PorB associates with mitochondria and prevents apoptosis of B cells, Jurkat cells and HeLa cells (Massari et al., 2000, Proc Natl Acad Sci USA 97: 9070-9075). This work examines if intact meningococci have a similar effect as purified porins. It was first determined that intact live meningococci do not induce apoptosis of HeLa cells and do not perturb mitochondrial physiology. This latter consideration is important as Neisserial porins affect the susceptibility of cells to apoptosis by preventing mitochondrial depolarization and cytochrome c release, events involved in the apoptosis cascade. Purified PorB or PorB from live bacteria were found to translocate into and interact with mitochondria. It was then determined whether treatment of HeLa cells with meningococci could prevent staurosporine-mediated apoptosis due to an effect of PorB on the mitochondrial parameters. Incubation of HeLa cells with live meningococci prevented staurosporine-induced apoptosis, as ascertained by measurements of mitochondrial potential, translocation of mitochondrial cytochrome c to the cytosol, caspases activation, and nuclear DNA degradation. These data are consistent with our previous findings that purified PorB associates with mitochondria and prevents apoptosis, and demonstrates that the mechanism by which whole meningococci protects cells from apoptosis is a result of direct interaction of neisserial porin with mitochondria.